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Background:

The treatment of intermediate and high grade non-Hodgkin's lymphoma has evolved over several decades. In the 1960s and early 1970s the primarytreatment was radiotherapy which cured many but not all patients. In thelate 1970s and into the 1980s many physicians dropped the use ofradiotherapy and treated patients exclusively with chemotherapy.However, chemotherapy alone was successful in curing only 30 to 40percent of patients with advanced disease. This led investigators tocombine chemotherapy and radiotherapy and several small trials reportedexcellent results utilizing both treatments. In 1988 the SouthwestOncology Group (SWOG) began a multi-institutional randomized trial comparing chemotherapy alone versus chemotherapy and radiotherapy. Theresults of this trial were published in the July 2 edition of the NewEngland journal of Medicine.

Methods:

The trial enrolled 401 patients with intermediate or high grade NHLwhich was 'localized' (i.e. the tumor was confined to one side of thediaphragm). In addition, patients with 'bulky' disease (i.e. a tumormass measuring >10cm or occupying > one-third of the chest diameter)were excluded. Patients were randomly assigned to receive eight cyclesof chemotherapy or three cycles of chemotherapy plus radiotherapy. Inboth arms the chemotherapy consisted of cyclophosphamide, doxirubicin,vincristine and prednisone (CHOP 1). Prednisone is administered orally onthe first five days of each cycle and the other chemotherapeuticmedications are given intravenously on the first day of each 21 daycycle.

Radiotherapy was started three weeks after the third cycle of CHOP.Doses ranged from 4000cGy to 5500cGy in 180 or 200cGy daily fractions.The final dose was at the discretion of the radiation oncologist. Ingeneral, only patients with residual tumor after 4000cGy receivedfurther dose, and the majority of patients received 4500Cgy-5000cGy. Thetreatment fields included the initial disease prior to biopsy andchemotherapy.

The study completed patient accrual in June 1995 with 201 patientsassigned to the chemotherapy arm and 200 receiving combined modalitytherapy. The two groups did not differ with respect to clinicalcharacteristics or risk factors.

Results:

The study found that patients treated with radiotherapy and chemotherapyfared significantly better than those treated with chemotherapy alone.The overall survival and progression free survival of patents on thecombined modality arm were 82 and 77%, respectively. This wassignificantly better than those who received chemotherapy alone whoseoverall survival and progression free survival were 72% and 64%,respectively.

Discussion:

Not only did the combination of the two treatments provide better tumorcontrol, but also caused less toxicity. Lives threatening toxic eventswere reported in 40% of patients receiving eight cycles of CHOP versus30% in the combined treatment group.

This study and a similar study reported by the Eastern CooperativeOncology Group (ECOG) will certainly make combined modality therapy thestandard of care for patients with localized intermediate or high gradeNHL.